casein-kinase-ii and fructose-1-6-diphosphate

Previous studies have shown that eIF-2B purified from rabbit reticulocytes binds ATP and that the binding is prevented by NADP+. Because NADP+ inhibits the activity of eIF-2B in in vitro reactions we have examined whether or not the activity of eIF-2B is modulated by ATP. In these studies, eIF-2B, purified from rat liver, was incubated with ATP prior to assay. We found that the activity of eIF-2B was inhibited with an IC50 of approximately 0.8 mM. The inhibition was not due to phosphorylation of the factor. However, the inhibition of eIF-2B activity caused by ATP could be prevented by coincubation with either NADPH or fructose-1,6-bisphosphate. The activity of eIF-2B was also inhibited following addition of either ATP or AMPPNP to a post-mitochondrial supernatant prepared from rat liver. Therefore, it is possible that the activity of eIF-2B might be allosterically regulated in vivo not only by changes in the redox state of pyridine dinucleotides but also by changes in the relative amounts of NADPH and ATP.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adenylyl Imidodiphosphate; Allosteric Regulation; Animals; Casein Kinase II; Fructosediphosphates; Guanine Nucleotide Exchange Factors; In Vitro Techniques; Liver; NADP; Oxidation-Reduction; Phosphorylation; Protein Serine-Threonine Kinases; Proteins; Rats